Neurotoxicity With Cilta-cel: Early Intervention Can Improve Outcomes in R/R Myeloma

Although chimeric antigen receptor (CAR) T-cell therapies like ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) can lead to neurologic adverse events (AEs) in patients with relapsed/refractory multiple myeloma, the toxicities can be managed without long-term effects as long as they are treated promptly, according to findings from CARTITUDE-2 presented at the European Hematology Association 2021 Virtual Congress.

“To date, more than 100 patients across the CARTITUDE study program have been dosed with cilta-cel. When implemented, patient [treatment] strategies have reduced the incidence of neurotoxicity, including movement and neurocognitive events,” said Hermann Einsele, MD, FRCP, professor and chair of the Department of Internal Medicine at the Julius Maximilians University of Würzburg in Germany, during a presentation of the study findings.

The open-label, phase 2, multicohort CARTITUDE-2 (NCT04133636) trial evaluated the efficacy and safety of cilta-cel in patients with multiple myeloma. For the purpose of studying adverse vents (AEs), the investigators analyzed cohort A, which involved patients with multiple myeloma who progressed after 1 to 3 lines of therapy, including a proteasome inhibitor or an immunomodulatory drug.

Eligible patients were adults with measurable disease and ECOG performance status of 0 or 1. Their disease had to be refractory to lenalidomide (Revlimid) and not previously treated with another BCMA-targeted drug.

Patients received cilta-cel (0.75 × 106 [range: 0.5-1.0 × 106] CAR+ viable T cells/kg) as a single infusion 5 to 7 days after the initiation of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days).

“Patient [treatment] strategies included more effective bridging therapy to reduce baseline tumor burden, early aggressive treatment of [cytokine release syndrome] and [immune effector cell-associated neurotoxicity], as well as handwriting assessment for early detection of symptoms of neurotoxicity,” Einsele said. “These strategies have been successfully implemented across the CARTITUDE program.”

At a median follow-up of 5.8 months (range, 2.5-9.8), 20 patients in cohort A received cilta-cel, of which 4 (20%) experienced at least 1 neurotoxicity. Three patients had grade 1/2 immune effector cell-associated neurotoxicity (ICANS) along with cytokine release syndrome. The median time to symptom onset was 8 days (range, 7-11), and, on average, symptoms lasted 2 days. Two patients received supportive measure for their ICANS, including levetiracetam and steroids.

One patient experienced isolated grade 2 facial paralysis on day 29. The patient recovered 51 days later after being treated with dexamethasone for 28 days. Overall, there were no movement or neurocognitive disorders reported within cohort A.

“Importantly, none of the patients in the cohort A of the CARTITUDE study experienced other neurotoxicities that were seen in CARTITUDE-1 (NCT03548207),” Einsele said.

Reference

Einsele H, Parekh S, Madduri D, et al. Incidence, mitigation, and management of neurologic adverse events in the phase 2 CARTITUDE-2 study of ciltacabtagene autoleucel in patients with multiple myeloma. Presented at: 2021 European Hematology Association Congress. June 9-17, 2021; virtual. Abstract EP1003.